Aaron Klug, a Lithuanian-born British chemist, was a central figure in structural molecular biology. He dedicated his career to understanding the intricate architecture and function of complex biological molecules. His pioneering work in electron microscopy profoundly advanced the ability to visualize and analyze these minute biological assemblies, revealing how essential biological machinery operates at a molecular level.
Early Life and Formative Research
Aaron Klug was born in Želva, Lithuania, in 1926, and moved to Durban, South Africa, at age two. He began his academic path studying medicine at the University of the Witwatersrand, but shifted to pure science, earning a Bachelor of Science in 1945. He continued at the University of Cape Town, receiving a Master of Science in 1946, where R.W. James introduced him to X-ray crystallography. This foundational training in physics fostered his interest in the organization of matter.
In 1949, Klug moved to Cambridge, England, completing his PhD in 1953 at the Cavendish Laboratory of Physics, focusing on phase changes in solids. His transition into biological research deepened when he joined Birkbeck College in London in 1954, where he met Rosalind Franklin. Franklin’s work on the tobacco mosaic virus sparked Klug’s lifelong interest in viruses, providing a new direction for his physics background to address biological questions.
Pioneering Structural Biology Techniques
Klug’s most significant contribution was his development of crystallographic electron microscopy. This innovative technique combined principles from X-ray diffraction with electron microscopy to overcome limitations in imaging complex biological structures. Traditional electron microscopes provided highly magnified two-dimensional images but struggled to resolve three-dimensional details or distinguish between layers of a specimen.
Klug devised a method to mathematically reconstruct three-dimensional structures from multiple two-dimensional electron micrographs taken at different angles. This approach allowed scientists to extract detailed structural information from biological samples too large or difficult to crystallize for conventional X-ray crystallography. His work enabled the visualization of biological objects with much higher resolution and accuracy, especially those with low contrast or susceptibility to radiation damage. The methods he developed were widely adopted globally, transforming the study of large molecular assemblies.
Unveiling Biological Structures
Applying his advanced techniques, Klug made fundamental discoveries about the structures of various biological entities. His initial work, alongside Rosalind Franklin, focused on the tobacco mosaic virus (TMV), a rod-shaped virus affecting plants. They elucidated its helical structure, showing how its RNA genetic material is embedded within a protein coat. Klug also studied the virus’s self-assembly process, proposing that the instructions for forming the complex structure are inherent in its individual protein units.
Klug’s research extended to transfer RNA (tRNA), a molecule essential for protein synthesis. In 1974, his group successfully determined the crystal structure of yeast phenylalanine tRNA, revealing its distinctive L-shaped three-dimensional fold. This structural insight helped explain how tRNA molecules function as adaptors, recognizing genetic codons and carrying specific amino acids.
Another significant area of his work was chromatin, the complex of DNA and proteins that forms chromosomes. Klug’s team investigated how DNA is packaged within the cell nucleus, determining the structure of the nucleosome core particle, the fundamental repeating unit of chromatin. Understanding this packaging influences how genetic information is accessed and regulated. Later in his career, Klug’s group also discovered zinc finger proteins, which are DNA-binding motifs involved in gene regulation.
Nobel Recognition and Enduring Legacy
Aaron Klug was awarded the Nobel Prize in Chemistry in 1982 for his groundbreaking contributions. The prize recognized his development of crystallographic electron microscopy and his successful elucidation of the structures of important nucleic acid-protein complexes. His innovative methodological work allowed for the visualization of previously unseen molecular details, transforming structural biology.
Beyond the Nobel Prize, Klug’s work laid a strong foundation for understanding fundamental molecular mechanisms in biology. His insights into protein-nucleic acid interactions influenced fields such as drug design, particularly through the study of zinc fingers and their potential for targeted therapies. He also advanced research into neurodegenerative diseases, including Alzheimer’s. Klug served as Director of the MRC Laboratory of Molecular Biology in Cambridge and as President of the Royal Society, demonstrating his leadership and mentorship within the scientific community. His collaborative spirit and ability to apply physics principles to biological problems inspired subsequent generations of scientists.